What are the main functions and efficacy of capisetinib tablets/caposetinib?

Capivasertib is a new type of oral small molecule kinase inhibitor that targets the AKT signaling pathway. It is one of the important research results in the current targeted therapy field of breast cancer. The AKT pathway belongs to the PI3K/AKT/mTOR signaling cascade system and plays a key role in the occurrence and development of various tumors. Especially in breast cancer patients who are hormone receptor positive, human epidermal growth factor receptor 2 (HER2) negative, and have PIK3CA, AKT1 or PTEN gene abnormalities, abnormal activation of AKT is often considered to be one of the main mechanisms of endocrine resistance. Therefore, the core function of caposetinib is to block AKT kinase activity, cut off the survival and proliferation signals of cancer cells from the source, and thereby inhibit the continued progression of tumors.

Currently, the main clinical indication of capositinib is to be used in combination with fulvestrant to treat patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer who have received endocrine therapy but whose disease has progressed. Especially in patients who carry key signaling pathway gene mutations such as PIK3CA, AKT1 or PTEN, this type of treatment is regarded as one of the typical targeted strategies under precision medicine. Studies have shown that capositinib can effectively reverse the resistance of tumor cells to traditional endocrine therapy and improve treatment response rate and progression-free survival.

From the mechanism of action, capositinib selectively inhibits the activity of three homologous protein kinasesAKT1, AKT2 and AKT3, blocking their phosphorylation of various downstream oncogenic proteins. This not only reduces the metabolic activity of tumor cells, but also inhibits angiogenesis and promotes cell apoptosis, thereby achieving comprehensive tumor suppression. At the same time, the drug also has a certain impact on the viability of tumor stem cells, which is expected to delay or prevent the recurrence of the disease.

In addition to breast cancer, the role of capositinib in a variety of other solid tumors has also attracted attention. Since PI3K/AKT signaling abnormalities are prevalent in ovarian cancer, endometrial cancer, prostate cancer, non-small cell lung cancer and other tumors, capositinib has also been widely explored in clinical trials for these indications. Especially in certain tumor types that are resistant to chemotherapy or other targeted drugs, the application of capositinib provides patients with new treatment options.

In terms of treatment strategy, capositinib is usually not used alone, but in combination with anti-hormone drugs such as fulvestrant, tamoxifen or aromatase inhibitors to improve the synergistic effect of targeted blockade. Through joint action, on the one hand, it can enhance the response toInhibition of the ER pathway, on the other hand, also prevents the AKT pathway from activating the "escape" mechanism from hormone therapy. This dual blockade strategy has shown good tolerability and efficacy synergy in clinical practice.

In addition, capositinib, as a small molecule oral drug, has the advantages of easy use by patients and easy monitoring of blood drug concentration. It is different from the broad-spectrum cytotoxicity caused by traditional chemotherapy. Although some adverse reactions may still occur during its use, such as diarrhea, hyperglycemia, rash, etc., they are generally manageable and can be dealt with through dose adjustment or supportive medication under the guidance of a doctor, which greatly reduces the risk of treatment interruption.

Reference materials:https://www.drugs.com/mtm/capivasertib.html